Rapid Increase in the use of CDK4/6 inhibitors as treatment for HR+/HER2- advanced breast cancer

November 2021 Clinical Practice Andrea Enguita

About two-thirds of advanced breast cancer (ABC) diagnoses are of the hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative (HR+/HER2) subtype (HR+/HER2 ABC). For years, the best available treatment plan for HR+/HER2 ABC patients has been endocrine therapy (ET) followed by chemotherapy. In August 2017, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with ET was introduced in the Netherlands. According to a new study published in International Journal of Cancer, two years after its implementation, half of the newly diagnosed patients received CDK4/6 inhibitors instead of chemotherapy.

Usually ET results in the development of endocrine resistance. When this occurs, several lines of chemotherapy follow as escalation strategy. Therefore, new targeted therapies are being designed to prolong the efficacy of ET while targeting activated cell cycle pathways. CDK4/6 inhibitors halt the proliferation of breast cancer cells by arresting progression from the G1 to the S phase during cell division, as CDK4 and CDK6 are critical drivers for the stimulation of cell cycle transcription genes.

In the current study, the authors evaluated the implementation of CDK4/6 inhibitors and changes in treatment choices. In order to do this, all patients diagnosed with HR+/HER2 ABC in 2009 to 2018 in seven hospitals were selected from the Southeast Netherlands Advanced Breast cancer (SONABRE) registry. The 2-year cumulative use of CDK4/6 inhibitors since reimbursement date (August 2017) was assessed using a competing-risk methodology in two cohorts. The first cohort included patients with ABC diagnosis between August 2017 and December 2018. The second cohort included patients with ABC diagnosis between 2009 and August 2017, who were still alive on August 1, 2017. In addition, treatment choices in the first three lines of therapy in calendar years 2009 to 2018 were evaluated for the total study population.

50% of newly diagnosed patients received CDK4/6 inhibitors two years after their implementation in 2017

Among patients diagnosed since August 2017 (first cohort; n=214), 50% (95% CI: 43-57) received CDK4/6 inhibitors within 2 years after diagnosis. Of eligible patients diagnosed before August 2017 (second cohort; n=417), 31% (95% CI: 27-36) received CDK4/6 inhibitors within 2 years following reimbursement. Another 20% of both cohorts were still CDK4/6 inhibitor naïve and on first-line therapy. The use of chemotherapy decreased in the first two lines of therapy between 2009 and 2018 (first-line: 29%-13%; second-line: 26%-19%).

Gaining insights into the implementation of CDK4/6 inhibitors in real-life is important to learn how they are used in daily clinical practice. These results show that the implementation rate of CDK4/6 inhibitors for HR+/HER2 disease has notably increased two years after implementation, and it is thought to further increase in the following years. In contrast, a decreased use of chemotherapy as first-line therapy is being observed since 2009. 


Meegdes M, Geurts SME, Erdkamp FLG et al. The implementation of CDK 4/6 inhibitors and its impact on treatment choices in HR+/HER2- advanced breast cancer patients: A study of the Dutch SONABRE Registry. Int J Cancer. 2021 Aug 30; ijc.33785